After finishing the human DNA analysis, structure analysis of bio molecules such as proteins, which are based on the gentic information, enables to find and develop new drugs.
IT-TOFMS offers fast structure analysis means for this purpose.
A protein analysis requires a high mass resolution of 5,000 or more, a high mass accuracy of 10 ppm, and a high sensitive multistage mass spectrometry. IT-TOFMS which is comprising two parts; an ion trap (IT) and a time-of-flight mass spectrometer (TOFMS), is expected to satisfy these requirements, because it determines a molecular structure using dissociation reactions in the ion trap and high mass resolution and a high mass accuracy mass analysis in the TOFMS. A 3-D quadrupole ion trap, as a said IT, stores ions stably with a quadrupole high-frequency voltage. The following operation method is described in “Practical Aspects of Ion Trap Mass Spectrometry,” R. E. March and F. J. Todd, John Wiley, 1995, page 34 to page 60. Sample ions are generated outside of the ion trap and trapped inside thereof. For the purpose the ion trap is filled with helium or other gas of several to several tens of m Torr. Incident ions are cooled by a collision with the gas and stored in the ion trap. The ion trap enables a removal of contaminations, a collision induced dissociation (CID) with the gas filling the ion trap, chemical reactions with the gas, or photochemical reactions. By detecting mass spectra after the dissociation as well as before that (multistage mass spectrometry), structure of the sample ions can be analyzed. Present mass spectrometers using Ion trap, however, is incapable of sufficiently achieving a resolution and a mass accuracy necessary for a protein analysis.
The following TOFMS operating method is described in “Time-of-Flight Mass Spectrometry,” R. J. Cotter, ACS professional reference book, 1997, page 1 to page 17. As shown in FIG. 6, the TOFMS comprises a pusher and an ion detector.
The pusher is an accelerator, which is composed of parallel plates and is applied high voltage pulses.
The plates are perforated or meshed so as to enable ions to pass through them. The ions accelerated by the pusher fly toward the ion detector. A multi channel plate (or MCP) is used for the detector. A flying time between the pusher and the MCP is measured. Since a distance between the pusher and the MCP and kinetic energy of ions are known, the mass of ions can be calculated. Furthermore, a reflectron is often used to get a high mass resolution because it corrects a spatial and energetic spread of ions in the pusher that decreases the mass resolution. The above method, however, is incapable of performing the multistage mass spectrometry and therefore structure analysis is difficult.
The following two conventional IT-TOFMS methods are well known as those with a combination of the ion trap and the TOF mass spectrometer. One is a coaxial-accelerator analyzer, which is well known in the literature, R. W. Purves and Liang Li: J. Am. Soc. Spectrom. 8 (1997), page 1,085 to page 1,093. In this prior art, the ion trap operates as a pusher as well as a trapping device. In other words, ions are accelerated by applying an voltage between two endcaps almost simultaneously with turning off an RF voltage applied to a ring voltage. The accelerated ions are ejected from a hole opened in the center of the endcap, and the ion detector located on an extension detects the ions. This method has an advantage that its configuration is simple. In the above method, however, the mass resolution and the mass accuracy were not good for ions having high mass numbers because of collision between the ions and the bath gas.
The other example of the IT-TOF MS is described in Japanese Unexamined Patent Publication (Kokai) No. 2001-297730. According to this, ions ejected from the ion trap are accelerated in a direction orthogonal to the traveling direction in a high vacuum unit. By spatial and energetic focusing by using ion focusing mechanism before accelerating the ions in the orthogonal direction, a high mass resolution and a high mass accuracy are achieved. The above method, however, causes another problem of a narrow mass range of ions detectable at a single pushing called mass window.
In other words, an operation of ejecting ions from the ion trap and pushing TOF is a mass separation. In other words, light ions arrive at the pusher earlier and heavy ions arrive later. Because the pusher size is limited, there is a mass range of ions pushable at a single ion ejection. Assuming that z0 is a distance from the center of the ion trap to the endcap, L is a distance from there to an entrance of the pusher, I is a pusher length, V is an acceleration voltage, m1 is the minimum ion mass number analyzable, and m2 is the maximum ion mass number analyzable, an analyzable mass-to-charge ratio, in other words, the mass window is given by:m2/m1={(L+1+2z0)/(L+2z0)}2Thereby, the mass window is substantially around 2. For example, a range of mass numbers 200 to 400 or 400 to 800 is a mass range of ions analyzable at a time. Therefore, to measure ions of mass numbers 200 to 4,000, the measurement need be performed five. Although these measurements can be performed in parallel, it decreases a throughput, which significantly reduces sensitivity. Therefore, desirably the mass window is equal to or more than 20.